IMPORTANT SAFETY INFORMATION FOR HUMIRA® (adalimumab)1
SERIOUS INFECTIONS
Patients treated with HUMIRA are at increased
risk for developing serious infections that
may lead to hospitalization or death. Most
patients who developed these infections were
taking concomitant immunosuppressants
such as methotrexate or corticosteroids.
Discontinue HUMIRA if a patient develops a
serious infection or sepsis.
Reported infections include:
• Active tuberculosis (TB), including
reactivation of latent TB. Patients with
TB have frequently presented with
disseminated or extrapulmonary disease.
Test patients for latent TB before HUMIRA
use and during therapy. Initiate treatment
for latent TB prior to HUMIRA use.
• Invasive fungal infections, including
histoplasmosis, coccidioidomycosis,
candidiasis, aspergillosis, blastomycosis,
and pneumocystosis. Patients with
histoplasmosis or other invasive fungal
infections may present with disseminated,
rather than localized, disease. Antigen and
antibody testing for histoplasmosis may
be negative in some patients with active
infection. Consider empiric anti-fungal
therapy in patients at risk for invasive
fungal infections who develop severe
systemic illness.
• Bacterial, viral, and other infections due
to opportunistic pathogens, including
Legionella and Listeria.
Carefully consider the risks and benefits of
treatment with HUMIRA prior to initiating
therapy in patients with chronic or recurrent
infection. Monitor patients closely for the
development of signs and symptoms of
infection during and after treatment with
HUMIRA, including the possible development
of TB in patients who tested negative for
latent TB infection prior to initiating therapy.
• Do not start HUMIRA in patients with an active
infection, including localized infections.
• Patients older than 65 years, patients with
co-morbid conditions, and/or patients taking
concomitant immunosuppressants may be at
greater risk of infection.
• Consider the risks and benefits of treatment
in patients with chronic or recurrent infection
or with underlying conditions which may
predispose them to infection, patients who
have been exposed to TB, patients with a
history of opportunistic infection, or patients
who have resided or traveled in regions where
TB or mycoses are endemic.
• Patients who develop a new infection should
undergo a prompt and complete diagnostic
workup, and appropriate antimicrobial therapy
should be initiated.
• Drug interactions with biologic products: A
higher rate of serious infections has been
observed in rheumatoid arthritis patients
treated with rituximab who received
subsequent treatment with a TNF blocker.

Concurrent use of HUMIRA with biologic
DMARDs (e.g., anakinra or abatacept) or other
TNF blockers is not recommended based on the
possible increased risk for infections and other
potential pharmacological interactions.
MALIGNANCY
Lymphoma and other malignancies, some
fatal, have been reported in children and
adolescent patients treated with TNF
blockers, including HUMIRA. Postmarketing
cases of hepatosplenic T-cell lymphoma
(HSTCL), a rare type of T-cell lymphoma, have
been reported in patients treated with TNF
blockers, including HUMIRA. These cases
have had a very aggressive disease course
and have been fatal. The majority of reported
TNF blocker cases have occurred in patients
with Crohn’s disease or ulcerative colitis and
the majority were in adolescent and young
adult males. Almost all of these patients
had received treatment with azathioprine
or 6-mercaptopurine concomitantly with
a TNF blocker at or prior to diagnosis. It is
uncertain whether the occurrence of HSTCL
is related to use of a TNF blocker or a TNF
blocker in combination with these other
immunosuppressants.
• Consider the risks and benefits of HUMIRA
treatment prior to initiating or continuing
therapy in a patient with known malignancy.
• More cases of malignancies were observed
among HUMIRA-treated patients compared to
control patients in clinical trials.
• Non-melanoma skin cancer (NMSC) has been
reported during clinical trials for HUMIRAtreated patients. Examine all patients,
particularly those with a history of prolonged
immunosuppressant or PUVA therapy, for
the presence of NMSC prior to and during
treatment with HUMIRA.
• In HUMIRA clinical trials, there was an
approximate 3-fold higher rate of lymphoma
than expected in the general U.S. population.
Patients with chronic inflammatory diseases,
particularly those with highly active disease
and/or chronic exposure to immunosuppressant
therapies, may be at higher risk of lymphoma
than the general population, even in the
absence of TNF blockers.
• Postmarketing cases of acute and chronic
leukemia were reported with TNF blocker
use. Approximately half of the postmarketing
cases of malignancies in children,
adolescents, and young adults receiving
TNF blockers were lymphomas; other cases
included rare malignancies associated with
immunosuppression and malignancies not
usually observed in children and adolescents.

HEPATITIS B VIRUS REACTIVATION
• Use of TNF blockers, including HUMIRA, may
increase the risk of reactivation of hepatitis B
virus (HBV) in patients who are chronic carriers.
Some cases have been fatal.
• Evaluate patients at risk for HBV infection for
prior evidence of HBV infection before initiating
TNF blocker therapy.
• Exercise caution in patients who are carriers
of HBV and monitor them during and after
treatment with HUMIRA.
• Discontinue HUMIRA and begin antiviral therapy
in patients who develop HBV reactivation.
• Exercise caution when considering resumption
of HUMIRA therapy after appropriate treatment
for HBV.
NEUROLOGIC REACTIONS
• TNF blockers, including HUMIRA, have been
associated in rare cases with new onset or
exacerbation of central nervous system and
peripheral demyelinating diseases, including
multiple sclerosis, optic neuritis, and GuillainBarré syndrome.
• Exercise caution when considering HUMIRA for
patients with these disorders.
HEMATOLOGIC REACTIONS
• Rare reports of pancytopenia, including
aplastic anemia, have been reported with
TNF blockers. Medically significant cytopenia
(e.g., thrombocytopenia, leukopenia) has been
infrequently reported with HUMIRA.
• Consider stopping HUMIRA in patients with
significant hematologic abnormalities.
CONGESTIVE HEART FAILURE
• Worsening or new onset congestive heart
failure (CHF) may occur.
• Exercise caution in patients with CHF and
monitor them carefully.
AUTOIMMUNITY
• Treatment with HUMIRA may result in the
formation of autoantibodies and, rarely, in
development of a lupus-like syndrome.
• Discontinue treatment if symptoms of a lupuslike syndrome develop.
IMMUNIZATIONS
• Patients on HUMIRA should not receive live
vaccines.
• It is recommended that pediatric patients,
if possible, be brought up to date with all
immunizations in agreement with current
immunization guidelines prior to initiating
HUMIRA therapy.

The last
thing you
want to
do is get
in his way
Help patients like him achieve
remission, with a self-injectable
biologic that can fit into his
busy life.

HUMIRA—the first and only biologic approved for children 6 years and older with
moderately to severely active CD that can be administered at home1
INDICATION1
HUMIRA is indicated for reducing signs and symptoms and inducing and maintaining clinical
remission in pediatric patients 6 years of age and older with moderately to severely active Crohn’s
disease who have had an inadequate response to corticosteroids or immunomodulators such as
azathioprine, 6-mercaptopurine, or methotrexate.
SELF-ADMINISTRATION CONSIDERATIONS1
Before HUMIRA is self-injected or administered by a caregiver, instruct patient or caregiver on
proper injection technique and monitor as necessary. Refer patient or caregiver to Medication
Guide for proper storage.

Please see adjacent page for additional Important Safety Information,
including BOXED WARNING on Serious Infections and Malignancy.

HUMIRA® (adalimumab)
WARNING: SERIOUS INFECTIONS AND MALIGNANCY
SERIOUS INFECTIONS
Patients treated with HUMIRA are at increased risk for developing
serious infections that may lead to hospitalization or death [see
Warnings and Precautions]. Most patients who developed these
infections were taking concomitant immunosuppressants such as
methotrexate or corticosteroids.
Discontinue HUMIRA if a patient develops a serious infection or
sepsis.
Reported infections include:
• Active tuberculosis (TB), including reactivation of latent TB.
Patients with TB have frequently presented with disseminated or
extrapulmonary disease. Test patients for latent TB before HUMIRA
use and during therapy. Initiate treatment for latent TB prior to
HUMIRA use.
• Invasive fungal infections, including histoplasmosis,
coccidioidomycosis, candidiasis, aspergillosis, blastomycosis, and
pneumocystosis. Patients with histoplasmosis or other invasive
fungal infections may present with disseminated, rather than
localized, disease. Antigen and antibody testing for histoplasmosis
may be negative in some patients with active infection. Consider
empiric anti-fungal therapy in patients at risk for invasive fungal
infections who develop severe systemic illness.
• Bacterial, viral and other infections due to opportunistic
pathogens, including Legionella and Listeria.
Carefully consider the risks and benefits of treatment with HUMIRA
prior to initiating therapy in patients with chronic or recurrent
infection.
Monitor patients closely for the development of signs and symptoms
of infection during and after treatment with HUMIRA, including the
possible development of TB in patients who tested negative for latent
TB infection prior to initiating therapy [see Warnings and Precautions
and Adverse Reactions].
MALIGNANCY
Lymphoma and other malignancies, some fatal, have been reported
in children and adolescent patients treated with TNF blockers
including HUMIRA [see Warnings and Precautions]. Post-marketing
cases of hepatosplenic T-cell lymphoma (HSTCL), a rare type of
T-cell lymphoma, have been reported in patients treated with TNF
blockers including HUMIRA. These cases have had a very aggressive
disease course and have been fatal. The majority of reported TNF
blocker cases have occurred in patients with Crohn’s disease or
ulcerative colitis and the majority were in adolescent and young
adult males. Almost all these patients had received treatment with
azathioprine or 6-mercaptopurine (6–MP) concomitantly with a
TNF blocker at or prior to diagnosis. It is uncertain whether the
occurrence of HSTCL is related to use of a TNF blocker or a TNF
blocker in combination with these other immunosuppressants [see
Warnings and Precautions].
INDICATIONS AND USAGE
Rheumatoid Arthritis
HUMIRA is indicated for reducing signs and symptoms, inducing major
clinical response, inhibiting the progression of structural damage, and
improving physical function in adult patients with moderately to severely
active rheumatoid arthritis. HUMIRA can be used alone or in combination
with methotrexate or other non-biologic disease-modifying anti-rheumatic
drugs (DMARDs).
Juvenile Idiopathic Arthritis
HUMIRA is indicated for reducing signs and symptoms of moderately to
severely active polyarticular juvenile idiopathic arthritis in patients
2 years of age and older. HUMIRA can be used alone or in combination with
methotrexate.
Psoriatic Arthritis
HUMIRA is indicated for reducing signs and symptoms, inhibiting the
progression of structural damage, and improving physical function in adult
patients with active psoriatic arthritis. HUMIRA can be used alone or in
combination with non-biologic DMARDs.
Ankylosing Spondylitis
HUMIRA is indicated for reducing signs and symptoms in adult patients with
active ankylosing spondylitis.
Adult Crohn’s Disease
HUMIRA is indicated for reducing signs and symptoms and inducing
and maintaining clinical remission in adult patients with moderately to
severely active Crohn’s disease who have had an inadequate response to
conventional therapy. HUMIRA is indicated for reducing signs and symptoms
and inducing clinical remission in these patients if they have also lost
response to or are intolerant to infliximab.
Pediatric Crohn’s Disease
HUMIRA is indicated for reducing signs and symptoms and inducing and
maintaining clinical remission in pediatric patients 6 years of age and
older with moderately to severely active Crohn’s disease who have had
an inadequate response to corticosteroids or immunomodulators such as
azathioprine, 6-mercaptopurine, or methotrexate.
Ulcerative Colitis
HUMIRA is indicated for inducing and sustaining clinical remission in adult
patients with moderately to severely active ulcerative colitis who have had
an inadequate response to immunosuppressants such as corticosteroids,
azathioprine or 6-mercaptopurine (6-MP). The effectiveness of HUMIRA
has not been established in patients who have lost response to or were
intolerant to TNF blockers.
Plaque Psoriasis
HUMIRA is indicated for the treatment of adult patients with moderate to
severe chronic plaque psoriasis who are candidates for systemic therapy
or phototherapy, and when other systemic therapies are medically less
appropriate. HUMIRA should only be administered to patients who will be
closely monitored and have regular follow-up visits with a physician
[see Boxed Warning and Warnings and Precautions].
CONTRAINDICATIONS
None.
WARNINGS AND PRECAUTIONS
Serious Infections
Patients treated with HUMIRA are at increased risk for developing serious

PROFESSIONAL BRIEF SUMMARY
CONSULT PACKAGE INSERT FOR FULL PRESCRIBING INFORMATION
infections involving various organ systems and sites that may lead to
hospitalization or death [see Boxed Warning]. Opportunistic infections
due to bacterial, mycobacterial, invasive fungal, viral, parasitic, or
other opportunistic pathogens including aspergillosis, blastomycosis,
candidiasis, coccidioidomycosis, histoplasmosis, legionellosis, listeriosis,
pneumocystosis and tuberculosis have been reported with TNF blockers.
Patients have frequently presented with disseminated rather than localized
disease.
The concomitant use of a TNF blocker and abatacept or anakinra was
associated with a higher risk of serious infections in patients with
rheumatoid arthritis (RA); therefore, the concomitant use of HUMIRA and
these biologic products is not recommended in the treatment of patients
with RA [see Warnings and Precautions and Drug Interactions].
Treatment with HUMIRA should not be initiated in patients with an active
infection, including localized infections. Patients greater than 65 years of
age, patients with co-morbid conditions and/or patients taking concomitant
immunosuppressants (such as corticosteroids or methotrexate), may be at
greater risk of infection. Consider the risks and benefits of treatment prior to
initiating therapy in patients:
• with chronic or recurrent infection;
• who have been exposed to tuberculosis;
• with a history of an opportunistic infection;
• who have resided or traveled in areas of endemic tuberculosis or
endemic mycoses, such as histoplasmosis, coccidioidomycosis, or
blastomycosis; or
• with underlying conditions that may predispose them to infection.
Tuberculosis
Cases of reactivation of tuberculosis and new onset tuberculosis infections
have been reported in patients receiving HUMIRA, including patients who
have previously received treatment for latent or active tuberculosis. Reports
included cases of pulmonary and extrapulmonary (i.e., disseminated)
tuberculosis. Evaluate patients for tuberculosis risk factors and test for
latent infection prior to initiating HUMIRA and periodically during therapy.
Treatment of latent tuberculosis infection prior to therapy with TNF blocking
agents has been shown to reduce the risk of tuberculosis reactivation
during therapy.
Consider anti-tuberculosis therapy prior to initiation of HUMIRA in patients
with a past history of latent or active tuberculosis in whom an adequate
course of treatment cannot be confirmed, and for patients with a negative
test for latent tuberculosis but having risk factors for tuberculosis infection.
Despite prophylactic treatment for tuberculosis, cases of reactivated
tuberculosis have occurred in patients treated with HUMIRA. Consultation
with a physician with expertise in the treatment of tuberculosis is
recommended to aid in the decision whether initiating anti-tuberculosis
therapy is appropriate for an individual patient.
Strongly consider tuberculosis in the differential diagnosis in patients who
develop a new infection during HUMIRA treatment, especially in patients
who have previously or recently traveled to countries with a high prevalence
of tuberculosis, or who have had close contact with a person with active
tuberculosis.
Monitoring
Closely monitor patients for the development of signs and symptoms
of infection during and after treatment with HUMIRA, including the
development of tuberculosis in patients who tested negative for latent
tuberculosis infection prior to initiating therapy. Tests for latent tuberculosis
infection may also be falsely negative while on therapy with HUMIRA.
Discontinue HUMIRA if a patient develops a serious infection or sepsis. For
a patient who develops a new infection during treatment with HUMIRA,
closely monitor them, perform a prompt and complete diagnostic workup
appropriate for an immunocompromised patient, and initiate appropriate
antimicrobial therapy.
Invasive Fungal Infections
If patients develop a serious systemic illness and they reside or travel in
regions where mycoses are endemic, consider invasive fungal infection in
the differential diagnosis. Antigen and antibody testing for histoplasmosis
may be negative in some patients with active infection. Consider appropriate
empiric antifungal therapy, taking into account both the risk for severe
fungal infection and the risks of antifungal therapy, while a diagnostic
workup is being performed. To aid in the management of such patients,
consider consultation with a physician with expertise in the diagnosis and
treatment of invasive fungal infections.
Malignancies
Consider the risks and benefits of TNF-blocker treatment including HUMIRA
prior to initiating therapy in patients with a known malignancy other
than a successfully treated non-melanoma skin cancer (NMSC) or when
considering continuing a TNF blocker in patients who develop a malignancy.
Malignancies in Adults
In the controlled portions of clinical trials of some TNF-blockers, including
HUMIRA, more cases of malignancies have been observed among TNFblocker-treated adult patients compared to control-treated adult patients.
During the controlled portions of 34 global HUMIRA clinical trials in adult
patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), ankylosing
spondylitis (AS), Crohn’s disease (CD), ulcerative colitis (UC) and plaque
psoriasis (Ps), malignancies, other than non-melanoma (basal cell and
squamous cell) skin cancer, were observed at a rate (95% confidence
interval) of 0.6 (0.38, 0.91) per 100 patient-years among 7304 HUMIRAtreated patients versus a rate of 0.6 (0.30, 1.03) per 100 patient-years
among 4232 control-treated patients (median duration of treatment of
4 months for HUMIRA-treated patients and 4 months for control-treated
patients). In 47 global controlled and uncontrolled clinical trials of HUMIRA
in adult patients with RA, PsA, AS, CD, UC, and Ps, the most frequently
observed malignancies, other than lymphoma and NMSC, were breast,
colon, prostate, lung, and melanoma. The malignancies in HUMIRA-treated
patients in the controlled and uncontrolled portions of the studies were
similar in type and number to what would be expected in the general U.S.
population according to the SEER database (adjusted for age, gender, and
race).
In controlled trials of other TNF blockers in adult patients at higher risk for
malignancies (i.e., patients with COPD with a significant smoking history
and cyclophosphamide-treated patients with Wegener’s granulomatosis), a
greater portion of malignancies occurred in the TNF blocker group compared
to the control group.
Non-Melanoma Skin Cancer
During the controlled portions of 34 global HUMIRA clinical trials in adult

patients with RA, PsA, AS, CD, UC, and Ps, the rate (95% confidence
interval) of NMSC was 0.7 (0.49, 1.08) per 100 patient-years among
HUMIRA-treated patients and 0.2 (0.08, 0.59) per 100 patient-years among
control-treated patients. Examine all patients, and in particular patients
with a medical history of prior prolonged immunosuppressant therapy or
psoriasis patients with a history of PUVA treatment for the presence of
NMSC prior to and during treatment with HUMIRA.
Lymphoma and Leukemia
In the controlled portions of clinical trials of all the TNF-blockers in adults,
more cases of lymphoma have been observed among TNF-blocker-treated
patients compared to control-treated patients. In the controlled portions
of 34 global HUMIRA clinical trials in adult patients with RA, PsA, AS, CD,
UC and Ps, 3 lymphomas occurred among 7304 HUMIRA-treated patients
versus 1 among 4232 control-treated patients. In 47 global controlled and
uncontrolled clinical trials of HUMIRA in adult patients with RA, PsA, AS,
CD, UC and Ps with a median duration of approximately 0.6 years, including
23,036 patients and over 34,000 patient-years of HUMIRA, the observed
rate of lymphomas was approximately 0.11 per 100 patient-years. This is
approximately 3-fold higher than expected in the general U.S. population
according to the SEER database (adjusted for age, gender, and race).
Rates of lymphoma in clinical trials of HUMIRA cannot be compared to
rates of lymphoma in clinical trials of other TNF blockers and may not
predict the rates observed in a broader patient population. Patients with
RA and other chronic inflammatory diseases, particularly those with highly
active disease and/or chronic exposure to immunosuppressant therapies,
may be at a higher risk (up to several fold) than the general population
for the development of lymphoma, even in the absence of TNF blockers.
Post-marketing cases of acute and chronic leukemia have been reported
in association with TNF-blocker use in RA and other indications. Even in
the absence of TNF-blocker therapy, patients with RA may be at a higher
risk (approximately 2-fold) than the general population for the development
of leukemia.
Malignancies in Pediatric Patients and Young Adults
Malignancies, some fatal, have been reported among children, adolescents,
and young adults who received treatment with TNF-blockers (initiation
of therapy ≤ 18 years of age), of which HUMIRA is a member [see Boxed
Warning]. Approximately half the cases were lymphomas, including
Hodgkin’s and non-Hodgkin’s lymphoma. The other cases represented a
variety of different malignancies and included rare malignancies usually
associated with immunosuppression and malignancies that are not usually
observed in children and adolescents. The malignancies occurred after a
median of 30 months of therapy (range 1 to 84 months). Most of the patients
were receiving concomitant immunosuppressants. These cases were
reported post-marketing and are derived from a variety of sources including
registries and spontaneous postmarketing reports.
Postmarketing cases of hepatosplenic T-cell lymphoma (HSTCL), a rare
type of T-cell lymphoma, have been reported in patients treated with
TNF blockers including HUMIRA [see Boxed Warning]. These cases have
had a very aggressive disease course and have been fatal. The majority
of reported TNF blocker cases have occurred in patients with Crohn’s
disease or ulcerative colitis and the majority were in adolescent and
young adult males. Almost all of these patients had received treatment
with the immunosuppressants azathioprine or 6-mercaptopurine (6–MP)
concomitantly with a TNF blocker at or prior to diagnosis. It is uncertain
whether the occurrence of HSTCL is related to use of a TNF blocker or a TNF
blocker in combination with these other immunosuppressants. The potential
risk with the combination of azathioprine or 6-mercaptopurine and HUMIRA
should be carefully considered.
Hypersensitivity Reactions
Anaphylaxis and angioneurotic edema have been reported following HUMIRA
administration. If an anaphylactic or other serious allergic reaction occurs,
immediately discontinue administration of HUMIRA and institute appropriate
therapy. In clinical trials of HUMIRA in adults, allergic reactions (e.g., allergic
rash, anaphylactoid reaction, fixed drug reaction, non-specified drug
reaction, urticaria) have been observed.
Hepatitis B Virus Reactivation
Use of TNF blockers, including HUMIRA, may increase the risk of reactivation
of hepatitis B virus (HBV) in patients who are chronic carriers of this virus.
In some instances, HBV reactivation occurring in conjunction with TNF
blocker therapy has been fatal. The majority of these reports have occurred
in patients concomitantly receiving other medications that suppress the
immune system, which may also contribute to HBV reactivation. Evaluate
patients at risk for HBV infection for prior evidence of HBV infection before
initiating TNF blocker therapy. Exercise caution in prescribing TNF blockers
for patients identified as carriers of HBV. Adequate data are not available
on the safety or efficacy of treating patients who are carriers of HBV with
anti-viral therapy in conjunction with TNF blocker therapy to prevent HBV
reactivation. In patients who develop HBV reactivation, stop HUMIRA and
initiate effective anti-viral therapy with appropriate supportive treatment.
The safety of resuming TNF blocker therapy after HBV reactivation is
controlled is not known.
Neurologic Reactions
Use of TNF blocking agents, including HUMIRA, has been associated with
rare cases of new onset or exacerbation of clinical symptoms and/or
radiographic evidence of central nervous system demyelinating disease,
including multiple sclerosis (MS) and optic neuritis, and peripheral
demyelinating disease, including Guillain-Barré syndrome. Exercise caution
in considering the use of HUMIRA in patients with preexisting or recentonset central or peripheral nervous system demyelinating disorders.
Hematological Reactions
Rare reports of pancytopenia including aplastic anemia have been
reported with TNF blocking agents. Adverse reactions of the hematologic
system, including medically significant cytopenia (e.g., thrombocytopenia,
leukopenia) have been infrequently reported with HUMIRA. The causal
relationship of these reports to HUMIRA remains unclear. Advise all patients
to seek immediate medical attention if they develop signs and symptoms
suggestive of blood dyscrasias or infection (e.g., persistent fever, bruising,
bleeding, pallor) while on HUMIRA. Consider discontinuation of HUMIRA
therapy in patients with confirmed significant hematologic abnormalities.
Use with Anakinra
Concurrent use of anakinra (an interleukin-1 antagonist) and another TNFblocker, was associated with a greater proportion of serious infections and
neutropenia and no added benefit compared with the TNF-blocker alone in
patients with RA. Therefore, the combination of HUMIRA and anakinra is not
recommended [see Drug Interactions].

Heart Failure
Cases of worsening congestive heart failure (CHF) and new onset CHF have
been reported with TNF blockers. Cases of worsening CHF have also been
observed with HUMIRA. Exercise caution when using HUMIRA in patients
who have heart failure and monitor them carefully.
Autoimmunity
Treatment with HUMIRA may result in the formation of autoantibodies and,
rarely, in the development of a lupus-like syndrome. If a patient develops
symptoms suggestive of a lupus-like syndrome following treatment with
HUMIRA, discontinue treatment [see Adverse Reactions].
Immunizations
In a placebo-controlled clinical trial of patients with RA, no difference was
detected in anti-pneumococcal antibody response between HUMIRA and
placebo treatment groups when the pneumococcal polysaccharide vaccine
and influenza vaccine were administered concurrently with HUMIRA.
Patients on HUMIRA may receive concurrent vaccinations, except for live
vaccines. No data are available on the secondary transmission of infection
by live vaccines in patients receiving HUMIRA.
It is recommended that pediatric patients, if possible, be brought up to date
with all immunizations in agreement with current immunization guidelines
prior to initiating HUMIRA therapy. Patients on HUMIRA may receive
concurrent vaccinations, except for live vaccines.
Use with Abatacept
In controlled trials, the concurrent administration of TNF-blockers and
abatacept was associated with a greater proportion of serious infections
than the use of a TNF-blocker alone; the combination therapy, compared
to the use of a TNF-blocker alone, has not demonstrated improved clinical
benefit in the treatment of RA. Therefore, the combination of abatacept
with TNF-blockers including HUMIRA is not recommended [see Drug
Interactions].
ADVERSE REACTIONS
The most serious adverse reactions described elsewhere in the labeling
include the following:
• Serious Infections [see Warnings and Precautions]
• Malignancies [see Warnings and Precautions]
Clinical Trials Experience
The most common adverse reaction with HUMIRA was injection site
reactions. In placebo-controlled trials, 20% of patients treated with HUMIRA
developed injection site reactions (erythema and/or itching, hemorrhage,
pain or swelling), compared to 14% of patients receiving placebo. Most
injection site reactions were described as mild and generally did not
necessitate drug discontinuation.
The proportion of patients who discontinued treatment due to adverse
reactions during the double-blind, placebo-controlled portion of studies
in patients with RA (i.e., Studies RA-I, RA-II, RA-III and RA-IV) was 7% for
patients taking HUMIRA and 4% for placebo-treated patients. The most
common adverse reactions leading to discontinuation of HUMIRA in these RA
studies were clinical flare reaction (0.7%), rash (0.3%) and pneumonia (0.3%).
Infections
In the controlled portions of the 34 global HUMIRA clinical trials in adult
patients with RA, PsA, AS, CD, UC and Ps, the rate of serious infections
was 4.6 per 100 patient-years in 7304 HUMIRA-treated patients versus a
rate of 3.1 per 100 patient-years in 4232 control-treated patients. Serious
infections observed included pneumonia, septic arthritis, prosthetic
and post-surgical infections, erysipelas, cellulitis, diverticulitis, and
pyelonephritis [see Warnings and Precautions].
Tuberculosis and Opportunistic Infections
In 47 global controlled and uncontrolled clinical trials in RA, PsA, AS, CD, UC
and Ps that included 23,036 HUMIRA-treated patients, the rate of reported
active tuberculosis was 0.22 per 100 patient-years and the rate of positive
PPD conversion was 0.08 per 100 patient-years. In a subgroup of 9396 U.S.
and Canadian HUMIRA-treated patients, the rate of reported active TB was
0.07 per 100 patient-years and the rate of positive PPD conversion was 0.08
per 100 patient-years. These trials included reports of miliary, lymphatic,
peritoneal, and pulmonary TB. Most of the TB cases occurred within the first
eight months after initiation of therapy and may reflect recrudescence of
latent disease. In these global clinical trials, cases of serious opportunistic
infections have been reported at an overall rate of 0.08 per 100 patientyears. Some cases of serious opportunistic infections and TB have been
fatal [see Warnings and Precautions].
Autoantibodies
In the rheumatoid arthritis controlled trials, 12% of patients treated with
HUMIRA and 7% of placebo-treated patients that had negative baseline ANA
titers developed positive titers at week 24. Two patients out of 3046 treated
with HUMIRA developed clinical signs suggestive of new-onset lupus-like
syndrome. The patients improved following discontinuation of therapy. No
patients developed lupus nephritis or central nervous system symptoms.
The impact of long-term treatment with HUMIRA on the development of
autoimmune diseases is unknown.
Liver Enzyme Elevations
There have been reports of severe hepatic reactions including acute liver
failure in patients receiving TNF-blockers. In controlled Phase 3 trials of
HUMIRA (40 mg SC every other week) in patients with RA, PsA, and AS with
control period duration ranging from 4 to 104 weeks, ALT elevations ≥ 3 x
ULN occurred in 3.5% of HUMIRA-treated patients and 1.5% of controltreated patients. Since many of these patients in these trials were also taking
medications that cause liver enzyme elevations (e.g., NSAIDS, MTX), the
relationship between HUMIRA and the liver enzyme elevations is not clear.
In a controlled Phase 3 trial of HUMIRA in patients with polyarticular JIA who
were 4 to 17 years, ALT elevations ≥ 3 x ULN occurred in 4.4% of HUMIRAtreated patients and 1.5% of control-treated patients (ALT more common
than AST); liver enzyme test elevations were more frequent among those
treated with the combination of HUMIRA and MTX than those treated with
HUMIRA alone. In general, these elevations did not lead to discontinuation of
HUMIRA treatment. No ALT elevations ≥ 3 x ULN occurred in the open-label
study of HUMIRA in patients with polyarticular JIA who were 2 to <4 years.
In controlled Phase 3 trials of HUMIRA (initial doses of 160 mg and 80 mg,
or 80 mg and 40 mg on Days 1 and 15, respectively, followed by 40 mg
every other week) in adult patients with CD with a control period duration
ranging from 4 to 52 weeks, ALT elevations ≥ 3 x ULN occurred in 0.9% of
HUMIRA-treated patients and 0.9% of control-treated patients. In the Phase
3 trial of HUMIRA in pediatric patients with Crohn’s disease which evaluated
efficacy and safety of two body weight based maintenance dose regimens
following body weight based induction therapy up to 52 weeks of treatment,
ALT elevations ≥ 3 x ULN occurred in 2.6% (5/192) of patients, of whom 4
were receiving concomitant immunosuppressants at baseline; none of these
patients discontinued due to abnormalities in ALT tests. In controlled Phase

3 trials of HUMIRA (initial doses of 160 mg and 80 mg on Days 1 and 15
respectively, followed by 40 mg every other week) in patients with UC with
control period duration ranging from 1 to 52 weeks, ALT elevations ≥3 x ULN
occurred in 1.5% of HUMIRA-treated patients and 1.0% of control-treated
patients. In controlled Phase 3 trials of HUMIRA (initial dose of 80 mg then
40 mg every other week) in patients with Ps with control period duration
ranging from 12 to 24 weeks, ALT elevations ≥ 3 x ULN occurred in 1.8% of
HUMIRA-treated patients and 1.8% of control-treated patients.
Immunogenicity
Patients in Studies RA-I, RA-II, and RA-III were tested at multiple time points
for antibodies to adalimumab during the 6- to 12-month period. Approximately
5% (58 of 1062) of adult RA patients receiving HUMIRA developed lowtiter antibodies to adalimumab at least once during treatment, which
were neutralizing in vitro. Patients treated with concomitant methotrexate
(MTX) had a lower rate of antibody development than patients on HUMIRA
monotherapy (1% versus 12%). No apparent correlation of antibody
development to adverse reactions was observed. With monotherapy, patients
receiving every other week dosing may develop antibodies more frequently
than those receiving weekly dosing. In patients receiving the recommended
dosage of 40 mg every other week as monotherapy, the ACR 20 response
was lower among antibody-positive patients than among antibody-negative
patients. The long-term immunogenicity of HUMIRA is unknown.
In patients with polyarticular JIA who were 4 to 17 years of age, adalimumab
antibodies were identified in 16% of HUMIRA-treated patients. In patients
receiving concomitant MTX, the incidence was 6% compared to 26% with
HUMIRA monotherapy. In patients with polyarticular JIA who were 2 to
<4 years of age or 4 years of age and older weighing <15 kg, adalimumab
antibodies were identified in 7% (1 of 15) of HUMIRA-treated patients, and
the one patient was receiving concomitant MTX.
In patients with AS, the rate of development of antibodies to adalimumab in
HUMIRA-treated patients was comparable to patients with RA.
In patients with PsA, the rate of antibody development in patients receiving
HUMIRA monotherapy was comparable to patients with RA; however, in
patients receiving concomitant MTX the rate was 7% compared to 1% in RA.
In adult patients with CD, the rate of antibody development was 3%.
In pediatric patients with Crohn’s disease, the rate of antibody development
in patients receiving HUMIRA was 3%. However, due to the limitation of the
assay conditions, antibodies to adalimumab could be detected only when
serum adalimumab levels were < 2 mcg/mL. Among the patients whose
serum adalimumab levels were < 2 mcg/mL (approximately 32% of total
patients studied), the immunogenicity rate was 10%.
In patients with moderately to severely active UC, the rate of antibody
development in patients receiving HUMIRA was 5%. However, due to the
limitation of the assay conditions, antibodies to adalimumab could be
detected only when serum adalimumab levels were < 2 mcg/mL. Among the
patients whose serum adalimumab levels were < 2 mcg/mL (approximately
25% of total patients studied), the immunogenicity rate was 20.7%.
In patients with Ps, the rate of antibody development with HUMIRA
monotherapy was 8%. However, due to the limitation of the assay
conditions, antibodies to adalimumab could be detected only when serum
adalimumab levels were < 2 mcg/mL. Among the patients whose serum
adalimumab levels were < 2 mcg/mL (approximately 40% of total patients
studied), the immunogenicity rate was 20.7%. In Ps patients who were on
HUMIRA monotherapy and subsequently withdrawn from the treatment, the
rate of antibodies to adalimumab after retreatment was similar to the rate
observed prior to withdrawal.
Other Adverse Reactions
Rheumatoid Arthritis Clinical Studies
The data described below reflect exposure to HUMIRA in 2468 patients,
including 2073 exposed for 6 months, 1497 exposed for greater than one
year and 1380 in adequate and well-controlled studies (Studies RA-I, RA-II,
RA-III, and RA-IV). HUMIRA was studied primarily in placebo-controlled
trials and in long-term follow up studies for up to 36 months duration.
The population had a mean age of 54 years, 77% were female, 91% were
Caucasian and had moderately to severely active rheumatoid arthritis. Most
patients received 40 mg HUMIRA every other week.
Table 1 summarizes reactions reported at a rate of at least 5% in patients
treated with HUMIRA 40 mg every other week compared to placebo and with
an incidence higher than placebo. In Study RA-III, the types and frequencies
of adverse reactions in the second year open-label extension were similar to
those observed in the one-year double-blind portion.
Table 1. Adverse Reactions Reported by ≥5% of Patients Treated
with HUMIRA During Placebo-Controlled Period of Pooled
RA Studies (Studies RA-I, RA-II, RA-III, and RA-IV)
HUMIRA 40 mg
Placebo
subcutaneous
Every Other Week
(N=705)
(N=690)
Adverse Reaction (Preferred Term)
Respiratory
Upper respiratory infection
17%
13%
Sinusitis
11%
9%
Flu syndrome
7%
6%
Gastrointestinal
Nausea
9%
8%
Abdominal pain
7%
4%
Laboratory Tests*
Laboratory test abnormal
8%
7%
Hypercholesterolemia
6%
4%
Hyperlipidemia
7%
5%
Hematuria
5%
4%
Alkaline phosphatase increased
5%
3%
Other
Headache
12%
8%
Rash
12%
6%
Accidental injury
10%
8%
Injection site reaction **
8%
1%
Back pain
6%
4%
Urinary tract infection
8%
5%
Hypertension
5%
3%
* Laboratory test abnormalities were reported as adverse reactions in
European trials
** Does not include injection site erythema, itching, hemorrhage, pain
or swelling

Juvenile Idiopathic Arthritis Clinical Studies
In general, the adverse reactions in the HUMIRA-treated patients in the
polyarticular juvenile idiopathic arthritis (JIA) trials (Studies JIA-I and JIA-II)
were similar in frequency and type to those seen in adult patients [see
Warnings and Precautions and Adverse Reactions]. Important findings and
differences from adults are discussed in the following paragraphs.
In Study JIA-I, HUMIRA was studied in 171 patients who were 4 to 17 years
of age, with polyarticular JIA. Severe adverse reactions reported in
the study included neutropenia, streptococcal pharyngitis, increased
aminotransferases, herpes zoster, myositis, metrorrhagia, and appendicitis.
Serious infections were observed in 4% of patients within approximately
2 years of initiation of treatment with HUMIRA and included cases of herpes
simplex, pneumonia, urinary tract infection, pharyngitis, and herpes zoster.
In Study JIA-I, 45% of patients experienced an infection while receiving
HUMIRA with or without concomitant MTX in the first 16 weeks of treatment.
The types of infections reported in HUMIRA-treated patients were generally
similar to those commonly seen in polyarticular JIA patients who are
not treated with TNF blockers. Upon initiation of treatment, the most
common adverse reactions occurring in this patient population treated with
HUMIRA were injection site pain and injection site reaction (19% and 16%,
respectively). A less commonly reported adverse event in patients receiving
HUMIRA was granuloma annulare which did not lead to discontinuation of
HUMIRA treatment.
In the first 48 weeks of treatment in Study JIA-I, non-serious hypersensitivity
reactions were seen in approximately 6% of patients and included primarily
localized allergic hypersensitivity reactions and allergic rash.
In Study JIA-I, 10% of patients treated with HUMIRA who had negative
baseline anti-dsDNA antibodies developed positive titers after 48 weeks of
treatment. No patient developed clinical signs of autoimmunity during the
clinical trial.
Approximately 15% of patients treated with HUMIRA developed mildto-moderate elevations of creatine phosphokinase (CPK) in Study JIA-I.
Elevations exceeding 5 times the upper limit of normal were observed in
several patients. CPK levels decreased or returned to normal in all patients.
Most patients were able to continue HUMIRA without interruption.
In Study JIA-II, HUMIRA was studied in 32 patients who were 2 to <4 years
of age or 4 years of age and older weighing <15 kg with polyarticular JIA.
The safety profile for this patient population was similar to the safety profile
seen in patients 4 to 17 years of age with polyarticular JIA.
In Study JIA-II, 78% of patients experienced an infection while receiving
HUMIRA. These included nasopharyngitis, bronchitis, upper respiratory tract
infection, otitis media, and were mostly mild to moderate in severity. Serious
infections were observed in 9% of patients receiving HUMIRA in the study
and included dental caries, rotavirus gastroenteritis, and varicella.
In Study JIA-II, non-serious allergic reactions were observed in 6% of
patients and included intermittent urticaria and rash, which were all mild
in severity.
Psoriatic Arthritis and Ankylosing Spondylitis Clinical Studies
HUMIRA has been studied in 395 patients with psoriatic arthritis (PsA) in two
placebo-controlled trials and in an open label study and in 393 patients with
ankylosing spondylitis (AS) in two placebo-controlled studies. The safety
profile for patients with PsA and AS treated with HUMIRA 40 mg every other
week was similar to the safety profile seen in patients with RA, HUMIRA
Studies RA-I through IV.
Adult Crohn’s Disease Clinical Studies
HUMIRA has been studied in 1478 adult patients with Crohn’s disease (CD)
in four placebo-controlled and two open-label extension studies. The safety
profile for adult patients with CD treated with HUMIRA was similar to the
safety profile seen in patients with RA.
Pediatric Crohn’s Disease Clinical Studies
HUMIRA has been studied in 192 pediatric patients with Crohn’s disease in
one double-blind study (Study PCD-I) and one open-label extension study. The
safety profile for pediatric patients with Crohn’s disease treated with HUMIRA
was similar to the safety profile seen in adult patients with Crohn’s disease.
During the 4 week open label induction phase of Study PCD-I, the most
common adverse reactions occurring in the pediatric population treated
with HUMIRA were injection site pain and injection site reaction (6% and
5%, respectively).
A total of 67% of children experienced an infection while receiving HUMIRA
in Study PCD-I. These included upper respiratory tract infection and
nasopharyngitis.
A total of 5% of children experienced a serious infection while receiving
HUMIRA in Study PCD-I. These included viral infection, device related sepsis
(catheter), gastroenteritis, H1N1 influenza, and disseminated histoplasmosis.
In Study PCD-I, allergic reactions were observed in 5% of children which
were all non-serious and were primarily localized reactions.
Ulcerative Colitis Clinical Studies
HUMIRA has been studied in 1010 patients with ulcerative colitis (UC) in two
placebo-controlled studies and one open-label extension study. The safety
profile for patients with UC treated with HUMIRA was similar to the safety
profile seen in patients with RA.
Plaque Psoriasis Clinical Studies
HUMIRA has been studied in 1696 patients with plaque psoriasis (Ps) in
placebo-controlled and open-label extension studies. The safety profile for
patients with Ps treated with HUMIRA was similar to the safety profile seen
in patients with RA with the following exceptions. In the placebo-controlled
portions of the clinical trials in Ps patients, HUMIRA-treated patients had a
higher incidence of arthralgia when compared to controls (3% vs. 1%).
Postmarketing Experience
The following adverse reactions have been identified during post-approval
use of HUMIRA. Because these reactions are reported voluntarily from a
population of uncertain size, it is not always possible to reliably estimate
their frequency or establish a causal relationship to HUMIRA exposure.
Gastrointestinal disorders: Diverticulitis, large bowel perforations including
perforations associated with diverticulitis and appendiceal perforations
associated with appendicitis, pancreatitis
General disorders and administration site conditions: Pyrexia
Hepato-biliary disorders: Liver failure, hepatitis
Immune system disorders: Sarcoidosis
Neoplasms benign, malignant and unspecified (including cysts and polyps):
Merkel Cell Carcinoma (neuroendocrine carcinoma of the skin)
Nervous system disorders: Demyelinating disorders (e.g., optic neuritis,
Guillain-Barré syndrome), cerebrovascular accident
Respiratory disorders: Interstitial lung disease, including pulmonary fibrosis,
pulmonary embolism

Skin reactions: Stevens Johnson Syndrome, cutaneous vasculitis, erythema
multiforme, new or worsening psoriasis (all sub-types including pustular and
palmoplantar), alopecia
Vascular disorders: Systemic vasculitis, deep vein thrombosis
DRUG INTERACTIONS
Methotrexate
HUMIRA has been studied in rheumatoid arthritis (RA) patients taking
concomitant methotrexate (MTX). Although MTX reduced the apparent
adalimumab clearance, the data do not suggest the need for dose
adjustment of either HUMIRA or MTX.
Biological Products
In clinical studies in patients with RA, an increased risk of serious infections
has been seen with the combination of TNF blockers with anakinra or
abatacept, with no added benefit; therefore, use of HUMIRA with abatacept
or anakinra is not recommended in patients with RA [see Warnings and
Precautions]. A higher rate of serious infections has also been observed
in patients with RA treated with rituximab who received subsequent
treatment with a TNF blocker. There is insufficient information regarding the
concomitant use of HUMIRA and other biologic products for the treatment
of RA, PsA, AS, CD, UC, and Ps. Concomitant administration of HUMIRA with
other biologic DMARDS (e.g., anakinra and abatacept) or other TNF blockers
is not recommended based upon the possible increased risk for infections
and other potential pharmacological interactions.
Live Vaccines
Avoid the use of live vaccines with HUMIRA [see Warnings and Precautions].
Cytochrome P450 Substrates
The formation of CYP450 enzymes may be suppressed by increased levels
of cytokines (e.g., TNFα, IL-6) during chronic inflammation. It is possible
for a molecule that antagonizes cytokine activity, such as adalimumab,
to influence the formation of CYP450 enzymes. Upon initiation or
discontinuation of HUMIRA in patients being treated with CYP450 substrates
with a narrow therapeutic index, monitoring of the effect (e.g., warfarin) or
drug concentration (e.g., cyclosporine or theophylline) is recommended and
the individual dose of the drug product may be adjusted as needed.
USE IN SPECIFIC POPULATIONS
Pregnancy
Pregnancy Category B
Risk Summary
Adequate and well controlled studies with HUMIRA have not been conducted
in pregnant women. Adalimumab is an IgG1 monoclonal antibody and
IgG1 is actively transferred across the placenta during the third trimester
of pregnancy. Adalimumab serum levels were obtained from ten women
treated with HUMIRA during pregnancy and eight newborn infants suggest
active placental transfer of adalimumab. No fetal harm was observed in
reproductive studies performed in cynomolgus monkeys. Because animal
reproductive studies are not always predictive of human response, this drug
should be used during pregnancy only if clearly needed.
Clinical Considerations
In general, monoclonal antibodies are transported across the placenta in a
linear fashion as pregnancy progresses, with the largest amount transferred
during the third trimester.
Human Data
In an independent clinical study conducted in ten pregnant women
with inflammatory bowel disease treated with HUMIRA, adalimumab
concentrations were measured in maternal blood as well as in cord (n=10)
and infant blood (n=8) on the day of birth. The last dose of HUMIRA was
given between 1 and 56 days prior to delivery. Adalimumab concentrations
were 0.16-19.7 μg/mL in cord blood, 4.28-17.7 μg/mL in infant blood, and
0-16.1 μg/mL in maternal blood. In all but one case, the cord blood level of
adalimumab was higher than the maternal level, suggesting adalimumab
actively crosses the placenta. In addition, one infant had levels at each
of the following: 6 weeks (1.94 μg/mL), 7 weeks (1.31 μg/mL), 8 weeks
(0.93 μg/mL), and 11 weeks (0.53 μg/mL), suggesting adalimumab can
be detected in the serum of infants exposed in utero for at least 3 months
from birth.
Nursing Mothers
Limited data from published literature indicate that adalimumab is present
in low levels in human milk and is not likely to be absorbed by a breastfed
infant. However, no data is available on the absorption of adalimumab from
breastmilk in newborn or preterm infants. Caution should be exercised when
HUMIRA is administered to a nursing woman.

Pediatric Use
Safety and efficacy of HUMIRA in pediatric patients for uses other than
polyarticular juvenile idiopathic arthritis (JIA) and pediatric Crohn’s
disease have not been established. Due to its inhibition of TNFα, HUMIRA
administered during pregnancy could affect immune response in the
in utero-exposed newborn and infant. Data from eight infants exposed to
HUMIRA in utero suggest adalimumab crosses the placenta [see Use in
Specific Populations]. The clinical significance of elevated adalimumab
levels in infants is unknown. The safety of administering live or liveattenuated vaccines in exposed infants is unknown. Risks and benefits
should be considered prior to vaccinating (live or live-attenuated) exposed
infants.
Post-marketing cases of lymphoma, including hepatosplenic T-cell
lymphoma and other malignancies, some fatal, have been reported among
children, adolescents, and young adults who received treatment with
TNF-blockers including HUMIRA [see Boxed Warning and Warnings and
Precautions].
Juvenile Idiopathic Arthritis
In Study JIA-I, HUMIRA was shown to reduce signs and symptoms of active
polyarticular JIA in patients 4 to 17 years of age [see Clinical Studies]. In
Study JIA-II, the safety profile for patients 2 to <4 years of age was similar
to the safety profile for patients 4 to 17 years of age with polyarticular JIA
[see Adverse Reactions]. HUMIRA has not been studied in patients with
polyarticular JIA less than 2 years of age or in patients with a weight below
10 kg.
The safety of HUMIRA in patients in the polyarticular JIA trials was generally
similar to that observed in adults with certain exceptions [see Adverse
Reactions].
Pediatric Crohn’s Disease
The safety and effectiveness of HUMIRA for reducing signs and
symptoms and inducing and maintaining clinical remission have been
established in pediatric patients 6 years of age and older with moderately
to severely active Crohn’s disease who have had an inadequate
response to corticosteroids or immunomodulators such as azathioprine,
6-mercaptopurine, or methotrexate. Use of HUMIRA in this age group
is supported by evidence from adequate and well-controlled studies of
HUMIRA in adults with additional data from a randomized, double-blind,
52-week clinical study of two dose levels of HUMIRA in 192 pediatric
patients (6 to 17 years of age) with moderately to severely active Crohn’s
disease [see Clinical Studies]. The safety and effectiveness of HUMIRA has
not been established in pediatric patients with Crohn’s disease less than
6 years of age.
Geriatric Use
A total of 519 RA patients 65 years of age and older, including 107 patients
75 years of age and older, received HUMIRA in clinical studies RA-I through
IV. No overall difference in effectiveness was observed between these
patients and younger patients. The frequency of serious infection and
malignancy among HUMIRA treated patients over 65 years of age was
higher than for those under 65 years of age. Because there is a higher
incidence of infections and malignancies in the elderly population, use
caution when treating the elderly.
OVERDOSAGE
Doses up to 10 mg/kg have been administered to patients in clinical trials
without evidence of dose-limiting toxicities. In case of overdosage, it is
recommended that the patient be monitored for any signs or symptoms
of adverse reactions or effects and appropriate symptomatic treatment
instituted immediately.
NONCLINICAL TOXICOLOGY
Carcinogenesis, Mutagenesis, Impairment of Fertility
Long-term animal studies of HUMIRA have not been conducted to
evaluate the carcinogenic potential or its effect on fertility. No clastogenic
or mutagenic effects of HUMIRA were observed in the in vivo mouse
micronucleus test or the Salmonella-Escherichia coli (Ames) assay,
respectively.
PATIENT COUNSELING INFORMATION
Patient Counseling
Provide the HUMIRA “Medication Guide” to patients or their caregivers, and
provide them an opportunity to read it and ask questions prior to initiation
of therapy and prior to each time the prescription is renewed. If patients
develop signs and symptoms of infection, instruct them to seek medical
evaluation immediately.
Advise patients of the potential benefits and risks of HUMIRA.

• Infections
Inform patients that HUMIRA may lower the ability of their immune
system to fight infections. Instruct patients of the importance of
contacting their doctor if they develop any symptoms of infection,
including tuberculosis, invasive fungal infections, and reactivation of
hepatitis B virus infections.
• Malignancies
Counsel patients about the risk of malignancies while receiving HUMIRA.
• Allergic Reactions
Advise patients to seek immediate medical attention if they experience
any symptoms of severe allergic reactions. Advise latex-sensitive patients
that the needle cap of the prefilled syringe contains latex.
• Other Medical Conditions
Advise patients to report any signs of new or worsening medical
conditions such as congestive heart failure, neurological disease,
autoimmune disorders, or cytopenias. Advise patients to report any
symptoms suggestive of a cytopenia such as bruising, bleeding, or
persistent fever.
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Knowing about
Central Precocious Puberty
can help your child.
Everyone starts puberty at a different time and progresses at a different rate. But generally puberty
begins around age 10 in girls and age 11 in boys.
Central precocious puberty (sometimes called “CPP” or “precocious puberty”) is a condition where
puberty starts too soon in children—usually before 8 years of years in girls and 9 years of age in
boys.1,2

If you start seeing early signs of puberty in your
child, you should talk with your child’s physician.
Pediatric Endocrinologists in Puerto Rico
Aguadilla
Dra. Michelle Gómez